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Autoimmune Status Epilepticus

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Autoimmune status epilepticus is a rare condition but one that has been increasingly recognized by neurologists and clinicians in the intensive care unit. As more cases are described in the literature and more antibody tests become commercially available, diagnosis is now feasible; however, early diagnosis remains a challenge. For practical purposes, status epilepticus may be considered as possibly autoimmune if it is refractory to anticonvulsant treatment and there is no other known cause; this may then lead to empiric immunomodulatory therapy. Major factors that raise the index of suspicion are recent cognitive or behavioral alterations, a history of malignancy or tumor, or presence of other neurological features. There is a lack of high level evidence in the literature for treatment of status epilepticus, and almost none for autoimmune encephalitis. Patients with autoimmune status epilepticus may be treated with immunomodulatory therapy, including steroids, intravenous immunoglobulin (IVIG), plasmapheresis (PLEX), and other immunosuppressive agents while maximizing their anticonvulsant therapy. For some patients, resective surgery may be necessary, such as hemispherectomy for Rasmussen’s encephalopathy. In the case of status epilepticus due to paraneoplastic autoantibodies, urgent and aggressive testing and treatment of a primary malignancy is needed. Importantly, any suspicion of autoimmune mediated status epilepticus should prompt the transfer of the patient to a specialized center with experience in refractory status epilepticus whenever possible.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. 1999;40(1):120–2.

    Article  PubMed  CAS  Google Scholar 

  2. Riviello JJ, Jr, Claassen J, Laroche SM, et al. Treatment of status epilepticus: an international survey of experts. Neurocrit Care. 2012;(in press).

  3. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17:3–23. Up to date guidelines for SE treatment in general, with standardized dosing and an explanation of emerging therapies.

    Article  PubMed  Google Scholar 

  4. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. 1998;338(14):970–6.

    Article  PubMed  CAS  Google Scholar 

  5. Lancaster E, Dalmau J. Neuronal autoantigens- pathogenesis, associated disorders and antibody testing. Nat Rev Neurol. 2012;8:380–90. A review of autoantibodies and underlying associations.

    Article  PubMed  CAS  Google Scholar 

  6. Rosenfeld MR, Dalmau JO. Paraneoplastic disorders of the CNS and autoimmune synaptic encephalitis. Continuum (Minneap Minn). 2012;18(2):366–83.

    Google Scholar 

  7. Jacobs DA, Fung KM, Cook NM, Schalepfer WW, Goldberg HI, Stecker MM. Complex partial status epilepticus associated with anti-Hu paraneoplastic syndrome. J Neurol Sci. 2003;213(1–2):77–82.

    Article  PubMed  Google Scholar 

  8. Shavit YB, Graus F, Probst A. Epilepsia partialis continua: a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis. Ann Neurol. 1999;45(2):255–8.

    Article  PubMed  CAS  Google Scholar 

  9. Kraker J. Treatment of anti-Ma2/Ta paraneoplastic syndrome. Curr Treat Options Neurol. 2009;11(1):46–51. A review in this format to address Ma2/Ta as a paraneoplastic disease.

    Article  PubMed  Google Scholar 

  10. Dalmau J. Status epilepticus due to paraneoplastic and nonparaneoplastic encephalitides. Epilepsia. 2009;50 Suppl 12:58–60.

    Article  PubMed  Google Scholar 

  11. Bien CG, Vincent A, Barnett MH, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain. 2012;135(Pt 5):1622–38.

    Article  PubMed  Google Scholar 

  12. Graus F, Saiz A, Lai M, et al. Neuronal surface antigen antibodies in limbic encephalitis: clinical-immunologic associations. Neurology. 2008;71(12):930–6.

    Article  PubMed  CAS  Google Scholar 

  13. Armangue T, Petit-Pedrol M, Dalmau J. Autoimmune encephalitis in children. J Child Neurol. 2012;(in press). A comprehensive overview of anti-NMDA, LE, Hashimoto’s and Rasmussen’s encephalitides as well as the less common syndromes.

  14. Dalmau J, Lancaster E, Martinez-Hernandez E, et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10(1):63–74. An important article which specifically addresses a treatment algorithm for NMDA receptor encephalitis.

    Article  PubMed  CAS  Google Scholar 

  15. Lai M, Huijbers MG, Lancaster E, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010;9(8):776–85.

    Article  PubMed  CAS  Google Scholar 

  16. Zuliani L, Graus F, Giometto B, et al. Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition. J Neurol Neurosurg Psychiatry. 2012;83(6):638–45. Excellent article which helps define the spectrum of neuronal surface antibody syndromes.

    Article  PubMed  Google Scholar 

  17. Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009;65(4):424–34.

    Article  PubMed  CAS  Google Scholar 

  18. Lancaster E, Lai M, Peng X, et al. Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen. Lancet Neurol. 2010;9(1):67–76.

    Article  PubMed  CAS  Google Scholar 

  19. Lancaster E, Martinez-Hernandez E, Titulaer MJ, et al. Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology. 2011;77(18):1698–701.

    Article  PubMed  CAS  Google Scholar 

  20. Granata T, Fusco L, Gobbi G, et al. Experience with immunomodulatory treatments in Rasmussen's encephalitis. Neurology. 2003;61(12):1807–10.

    Article  PubMed  CAS  Google Scholar 

  21. Andrews PI, Dichter MA, Berkovic SF, et al. Plasmapheresis in Rasmussen's encephalitis. Neurology. 1996;46(1):242–6.

    Article  PubMed  CAS  Google Scholar 

  22. Vadera S, Moosa AN, Jehi L, et al. Reoperative hemispherectomy for intractable epilepsy: a report of 36 patients. Neurosurgery. 2012;71(2):388,92. discussion 392–3

    Article  Google Scholar 

  23. Pulsifer MB, Brandt J, Salorio CF. The cognitive outcome of hemispherectomy in 71 children. Epilepsia. 2004;45(3):243–54.

    Article  PubMed  Google Scholar 

  24. de Holanda NC, de Lima DD, Cavalcanti TB, et al. Hashimoto's encephalopathy: systematic review of the literature and an additional case. J Neuropsychiatry Clin Neurosci. 2011;23(4):384–90.

    Article  PubMed  Google Scholar 

  25. Duffey P, Yee S, Reid IN, Bridges LR. Hashimoto's encephalopathy: postmortem findings after fatal status epilepticus. Neurology. 2003;61(8):1124–6.

    Article  PubMed  Google Scholar 

  26. Aydin-Ozemir Z, Tuzun E, Baykan B, et al. Autoimmune thyroid encephalopathy presenting with epilepsia partialis continua. Clin EEG Neurosci. 2006;37(3):204–9.

    Article  PubMed  Google Scholar 

  27. Tsai MH, Lee LH, Chen SD, et al. Complex partial status epilepticus as a manifestation of Hashimoto's encephalopathy. Seizure. 2007;16:713–6.

    Article  PubMed  Google Scholar 

  28. Saiz A, Blanco Y, Sabater L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131:2553–63.

    Article  PubMed  Google Scholar 

  29. Malter MP, Helmstaedter C, Urbach H, et al. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol. 2010;67(4):470–8.

    Article  PubMed  Google Scholar 

  30. Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7:1091–8.

    Article  PubMed  CAS  Google Scholar 

  31. Mathew RM, Vandenberghe R, Garcia-Merino A, et al. Orchiectomy for suspected microscopic tumor in patients with anti-Ma2-associated encephalitis. Neurology. 2007;68:900–5.

    Article  PubMed  CAS  Google Scholar 

  32. Prasad K, Al-Roomi K, Krishnan Pudukode R, Sequeira R. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. 2005;(4).

  33. Malamiri RA, Ghaempanah M, Khosroshahi N, et al. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial. Eur J Paediatr Neurol. 2012;16(5):536–41.

    Article  PubMed  Google Scholar 

  34. Towne AR, Garnett LK, Waterhouse EJ, et al. The use of topiramate in refractory status epilepticus. Neurology. 2003;60(2):332–4.

    Article  PubMed  CAS  Google Scholar 

  35. Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia. 2002;43(2):146–53.

    Article  PubMed  CAS  Google Scholar 

  36. Miro J, Toledo M, Santamarina E, et al. Efficacy of intravenous lacosamide as an add-on treatment in refractory status epilepticus: a multicentric prospective study. Seizure. 2012;(in press).

  37. Li J, Saldivar C, Maganti RK. Plasma exchange in cryptogenic new onset refractory status epilepticus. Seizure. 2012;(in press).

  38. Vincent A, Buckley C, Schott JM, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. 2004;127(Pt 3):701–12.

    PubMed  Google Scholar 

  39. Vernino S, O'Neill BP, Marks RS, et al. Immunomodulatory treatment trial for paraneoplastic neurological disorders. Neuro Oncol. 2004;6(1):55–62.

    Article  PubMed  Google Scholar 

  40. Holzer FJ, Rossetti AO, Heritier-Barras AC, et al. Antibody-mediated status epilepticus: a retrospective multicenter survey. Eur Neurol. 2012;68(5):310–7. A series of thirteen patients collected from centers in Europe, mostly NMDA R encephalitis, with outcomes and treatments.

    Article  PubMed  CAS  Google Scholar 

  41. Goldenholz DM, Wong VS, Bateman LM, et al. Treatment of gamma-aminobutyric AcidBReceptor-antibody autoimmune encephalitis with oral corticosteroids. Arch Neurol. 2012;69(8):1061–3.

    Article  PubMed  Google Scholar 

  42. Grujic J, Bien CG, Pollo C, Rossetti AO. Vagus nerve stimulator treatment in adult-onset Rasmussen's encephalitis. Epilepsy Behav. 2011;20(1):123–5.

    Article  PubMed  Google Scholar 

  43. Loddenkemper T, Goodkin HP. Treatment of pediatric status epilepticus. Curr Treat Options Neurol. 2011;13(6):560–73.

    Article  PubMed  Google Scholar 

  44. Bien CG, Tiemeier H, Sassen R, et al. Rasmussen encephalitis: incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins. Epilepsia. 2013;54:543–50.

    Article  PubMed  CAS  Google Scholar 

  45. Honnorat J, Didelot A, Karantoni E, et al. Autoimmune limbic encephalopathy and anti-Hu antibodies in children without cancer. Neurology. 2013;80(24):2226–2232.

    Google Scholar 

  46. Stitch O, Klages E, Bischler P, et al. SOX1 antibodies in sera from patients with paraneoplastic neurological syndromes. Acta Neurol Scand: 2012;125:326–331.

    Google Scholar 

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Conflict of Interest

Carla LoPinto-Khoury has received speaker honoraria from UCB.

Michael R. Sperling has served as a consultant for Acorda Therapeutics and electroCore.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Neurology, Drexel College of Medicine, New College Building, 7th Floor, 245 North 15th Street, Philadelphia, PA, 19102, USA

    Carla LoPinto-Khoury MD

  2. Department of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, 901 Walnut Street, Suite 400, Philadelphia, PA, 19107, USA

    Michael R. Sperling MD

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  1. Carla LoPinto-Khoury MD
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  2. Michael R. Sperling MD
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Correspondence to Carla LoPinto-Khoury MD.

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LoPinto-Khoury, C., Sperling, M.R. Autoimmune Status Epilepticus. Curr Treat Options Neurol 15, 545–556 (2013). https://doi.org/10.1007/s11940-013-0252-7

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